The Role of Histopathology and Immunohistochemistry in the Diagnosis of Neuroendocrine Biliary Duct Tumor.

Neuroendocrine tumors of the biliary tract are rare entities developed form Kulchitsky cells which undergo a process of malignant transformation. However, the differential diagnostic between neuroendocrine tumors of the biliary tract and hilar cholangiocarcinoma is very difficult to be established during the preoperative workup; therefore, most patients are submitted to surgery with radical intent and the final diagnostic remains to be confirmed through histopathological and immunohistochemistry studies of the specimen of resection. We present the case of a 60 year old patient who was submitted to en bloc extended right hepatectomy (including segment IV and caudate lobe) with extra hepatic biliary tree resection and left hepatic duct preservation, left cholangiojejunostomy (Roux-En-Y technique), celiac and common hepatic arteries lymphadenectomy and segmental portal vein resection with end-to-end anastomosis for a tumor of the biliary carrefour extended to the right biliary duct and invading the portal vein. The histopathological and immunohistochemistry studies confirmed the presence of a grade 1 neuroendocrine tumor, the staining being positive for Chromogranin A, Neuron-Specific Enolase (NSE) and Ki-67 (1% nuclear positive). At 24 months follow-up the patient is free of recurrent disease.

Diagnosis, morphopathological profile and treatment of mucinous cystadenoma of the pancreas - a single center experience.

AIM: Pancreatic mucinous cystadenoma (MCA) occurs almost exclusively in perimenopausal women and represents between 10% and 45% of cystic neoplasm of the pancreas, being considered a premalignant lesion. MATERIALS AND METHODS: From 1983 to 2017, 31 patients underwent surgery for MCA of the pancreas in our Center. The median age was 47 years (range 17-81 years). All data were obtained retrospectively. RESULTS: The female∕male gender ratio was 14.5∕1. Most of the patients (90.3%) were symptomatic. The most common clinical manifestation was non-specific abdominal pain (58.06%), followed by fatigue and vomiting. The median cyst size was 7 cm, with a range between 2 cm and 15 cm. There were 35 procedures in 31 patients (in four patients the resection was preceded by a drainage procedure). From the 28 resections, most of them (89.28%) were performed by an open approach; a minimal invasive approach was used in three patients (robotic - two; laparoscopic - one). Most of the resections (82.14%) were distal pancreatectomies. In all cases, the final diagnosis was based on histological examination that revealed columnar epithelium and ovarian-type stroma. Postoperative complications occurred in 10 (34.48%) patients. Postoperative mortality was 3.44% (one patient) by septic shock secondary to acute postoperative pancreatitis. CONCLUSIONS: MCAs represent a rare pancreatic pathology with challenging diagnostic and therapeutic implications. Multi-detector computed tomography (MDCT) scan, endoscopic ultrasound (EUS) and magnetic resonance imaging (MRI)∕magnetic resonance cholangiopancreatography (MRCP) are useful in the differential diagnosis with other pancreatic fluid collections and treatment. Oncological surgical resections are recommended. Histopathological examination establishes the final diagnosis. The most common postoperative complication is pancreatic fistula.

Resection of Concomitant Hepatic and Extrahepatic Metastases from Colorectal Cancer - A Worthwhile Operation?

Background: The benefit of hepatic resection in case of concomitant colorectal hepatic and extrahepatic metastases (CHEHMs) is still debatable. The purpose of this study is to assess the results of resection of hepatic and extrahepatic metastases in patients with CHEHMs in a high-volume center for both hepatobiliary and colorectal surgery and to identify prognostic factors that correlate with longer survival in these patients. METHOD: It was performed a retrospective analysis of 678 consecutive patients with liver resection for colorectal cancer metastases operated in a single Centre between April 1996 and March 2016. Among these, 73 patients presented CHEHMs. Univariate analysis was performed to identify the risk factors for overall survival (OS) in these patients. Results: There were 20 CHMs located at the lymphatic node level, 20 at the peritoneal level, 12 at the ovary and lung level, 12 presenting as local relapses and 9 other sites. 53 curative resections (R0) were performed. The difference in overall survival between the CHEHMs group and the CHMs group is statistically significant for the entire groups (p 0.0001), as well as in patients who underwent R0 resection (p 0.0001). In CHEHMs group, the OS was statistically significant higher in patients who underwent R0 resection vs. those with R1/R2 resection (p=0.004). Three variables were identified as prognostic factors for poor OS following univariate analysis: 4 or more hepatic metastases, major hepatectomy and the performance of operation during first period of the study (1996 - 2004). There was a tendency toward better OS in patients with ovarian or pulmonary location of extrahepatic disease, although the difference was not statistically significant. CONCLUSION: In patients with concomitant hepatic and extrahepatic metastases, complete resection of metastatic burden significantly prolong survival. The patients with up to 4 liver metastases, resectable by minor hepatectomy benefit the most from this aggressive onco-surgical management.

The Romanian National Program for Liver Transplantation - 852 Procedures in 815 Patients over 17 Years (2000-2017): A Continuous Evolution to Success.

Background: Liver transplantation (LT) has become an established treatment for end-stage liver disease, with more than 20.000 procedures yearly worldwide. The aim of this study was to analyze the results of Romanian National Program of LT. Methods: Between April 2000 and April 2017, 817 pts received 852 LTs in Romania. Male/female ratio was 487/330, while adult/pediatric ratio was 753/64, with a mean age of 46 years (median 50 yrs; range 7 months - 68 yrs). Main LT indications were HBV cirrhosis (230 pts; 28.2%), HCC (173 pts; 21.2%), and HCV cirrhosis (137 pts; 16.8%). Waiting time and indications for LT, patient and donor demographics, graft features, surgical procedures, and short and long-term outcomes were analyzed. Results: DDLT was performed in 682 pts (83.9%): whole LT in 662 pts (81%), split LT in 16 pts (2.3%), reduced LT in 2 pts (0.2%), and domino LT in 1 pts (0.1%). LDLT was performed in 135 pts (16.5%): right hemiliver in 93 pts (11.4%), left lateral section in 28 pts (3.4%), left hemiliver in 8 pts (1%), left hemiliver with segment 1 in 4 pts (0.5%), and dual graft LDLT in 2 pts (0.2%). Overall major morbidity rate was 31.4% (268 pts), while perioperative mortality was 7.9% (65 pts). Retransplantation rate was 4.3% (35 pts): 27 whole LTs, 3 reduced LTs, 3 split LTs, and 2 LDLT. Long-term overall 1-, 3-, and 5-year estimated survival rates for patients were 87.9%, 81.5%, and 79.1%, respectively. One-, 3-, and 5-year overall mortality on waiting list also decreased significantly over time from 31.4%, 54.1% and 63.5%, to 4.4%, 13.9% and 23.6%, respectively. Conclusions: The Romanian National program for liver transplantation addresses all causes of acute and chronic liver failure or liver tumors in adults and children, using all surgical techniques, with good long-term outcome. The program constantly evolved over time, leading to decreased mortality rate on the waiting list.

Liver Resections in a High-Volume Center: Form Standard Procedures to Extreme Surgery and Ultrasound-guided Resections.

Background: Liver resection (LR) is the treatment of choice for most benign and malignant focal liver lesions, as well as in selected patients with liver trauma. Few other therapies can compete with LR in selected cases, such as liver transplantation in hepatocellular carcinoma (HCC) and ablative therapies in small HCCs or liver metastases. The present paper analyses a single center experience in LR, reviewing the indications of LR, the operative techniques and their short-term results. MATERIAL AND METHOD: Between January 2000 and December 2016, in "œDan Setlacec" Center of General Surgery and Liver Transplantation were performed 3165 LRs in 3016 patients, for pathologic conditions of the liver. In the present series, liver resections for living-donor liver transplantation were excluded. The median age of the patients was 56 years (mean 58 years; range 1-88), with male/female ratio 1524/1492 and adult/pediatric patient ratio 2973/43. Results: Malignant lesions were the main indication for LR (2372 LRs; 74.9%). Among these, colorectal liver metastases were the most frequent indication (952 LRs; 30.1%), followed by hepatocellular carcinoma (575 patients, 18.2%). The highest number of resected tumors per patient was 21, and the median diameter of the largest tumor was 40 mm (mean 51 mm; range 3-250). Major resections rate was 18.6% (588 LRs) and anatomical LRs were performed in 789 patients (24.9%). The median operative time was 180 minutes (mean 204 minutes; range 45-920). The median blood loss was 500 ml (mean 850 ml; range 500-9500), with a transfusion rate of 41.6% (1316 LRs). The morbidity rate was 40.1% (1270 LRs) and the rate of major complications (Dindo-Clavien IIIa or more) was 13.2% (418 LRs). Mortality rate was 4.2% (127 pts). CONCLUSION: LRs should be performed in specialized high-volume centers to achieve the best results (low morbidity and mortality rates).

Comparative Analysis between Simultaneous Resection and Staged Resection for Synchronous Colorectal Liver Metastases - A Single Center Experience on 300 Consecutive Patients.

Introduction: In synchronous colorectal liver metastases (SCLMs), simultaneous resection (SR) of the primary tumor and liver metastases has not gained wide acceptance. Most authors prefer staged resections (SgR), especially in patients presenting rectal cancer or requiring major hepatectomy. Methods: Morbidity, mortality, survival rates and length of hospital stay were compared between the two groups of patients (SR vs. SgR). A subgroup analysis was performed for patients with similar characteristics (e.g. rectal tumor, major hepatectomy, bilobar metastases, metastatic lymph nodes, preoperative chemotherapy). Results: Between 1995 and 2016, SR was performed in 234 patients, while 66 patients underwent SgR. Comparative morbidity (41% vs. 31.8%, respectively, p = 0.1997), mortality (3.8% vs. 3%, respectively, p = 1) and overall survival rates (85.8%, 51.3% and 30% vs. 87%, 49.6% and 22.5%, at 1-, 3- and 5-years, respectively, p = 0.386) were similar between the SR and SgR group. Mean hospital stay was significantly shorter in patients undergoing SR than SgR (15.11 ‚+- 8.60 vs. 19.42 ‚+- 7.36 days, respectively, p 0.0001). The characteristics of SR and SgR groups were similar, except the following parameters: rectal tumor (34.1% vs. 19.7%, respectively, p = 0.0245), metastatic lymph nodes (68.1% vs. 86.3%, respectively, p = 0.0383), bilobar liver metastases (22.6% vs. 37.8%, respectively, p = 0.0169), major hepatectomies (13.2% vs. 30.3%, respectively, p= 0.0025) and neo-adjuvant chemotherapy (13.2% vs. 77.2%, respectively, p 0.0001). A comparative analysis of morbidity, mortality and survival rates between SR and SgR was performed for subgroups of patients presenting these parameters. In each of these subgroups, SR was associated with similar morbidity, mortality and survival rates compared with SgR (p value 0.05). CONCLUSION: In patients with SCLMs, SR provides similar short-term and long-term outcomes as SgR, with a shorter hospital stay. Therefore, in most patients with SCLMs, SR might be considered the treatment of choice.

Curative Intent Treatment of Hepatocellular Carcinoma - 844 Cases Treated in a General Surgery and Liver Transplantation Center.

Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR.

Fibrolamellar hepatocellular carcinoma with ovarian metastasis - an unusual presentation.

AIM: Fibrolamellar carcinoma (FLC) has been considered a distinct clinical entity vs. hepatocellular carcinoma, with respect to its epidemiology, etiology, and prognosis. CASE PRESENTATION: We describe the unusual case of a 23-year-old female patient with FLC and ovarian (Krukenberg) and peritoneal metastases, clinically mimicking an ovarian carcinoma. Multiple recurrences occurred despite initial R0 resection and chemotherapy, requiring surgical treatment. The patient survived five years and died from generalized disease. DISCUSSION: The particularities of our case are discussed by comparison with the other two similar cases and other date from the literature. CONCLUSIONS: To our knowledge, the ovarian involvement encountered in our case is the third case published in literature, being explained by the superficial location of the liver tumor.

Bouveret Syndrome - An Exceptional Complication of a Very Frequent Disease.

The Bouveret syndrome is an exceptional complication of the gallbladder lithiasis. Hereby it is described the case of a patient with a history of gallstones complicated on the long-term outcome with gastric outlet obstruction, due to a large gallstone of the duodenum, migrated via a cholecysto-duodenal fistula. The clinical, radiological features and the patient management are described.

Strategies to convert to resectability the initially unresectable colorectal liver metastases.

BACKGROUND/AIMS: Because only 25% of colorectal liver metastases (CRLM) are initially resectable, we used several therapeutic strategies to convert to resectability some of the initially unresectable CRLM. Our results are presented herein. METHODOLOGY: The therapeutical strategies were: (A) Liver resection after portal vein ligation--10 patients; (B) Staged liver resection with portal vein ligation--3 patients; (C) Staged liver resection without portal vein ligation--3 patients; (D) Resection after "do wn-sizing" of CRLM by conversion chemotherapy--3 patients; (E) Resection associated with radiofrequency ablation--9 patients. RESULTS: The resectability rate was 60% (6/10) in group A and 66% (2/3) in groups B and C. For the entire series, the morbidity and mortality rates were 50% (11/22 patients) and 4.5% (1/22 patients), respectively. The overall one-, two-, and three-year survival rates of the entire group of patients rendered to resectability were 80.1%, 44.8% and 35.9%, respectively. CONCLUSIONS: In selected patients with initially unresectable CRLM, "two-stage" hepatectomies (with/without PVE/PVL) can be performed safely, achieving long-term survival. Liver resection may be achieved safely after conversion chemotherapy in some previously unresectable patients, with considerable survival benefit. RFA could be associated with liver resection to increase the number of patients eligible for complete removal and ablation of their CRLM.

Gallbladder adenoma with focal adenocarcinoma.

The majority of polypoid lesions of the gallbladder are cholesterolosis pseudopolyps. True neoplastic GB polyps are represented mainly by adenomas. The case of a 52-year old male patient with an adenomatous polyp of the GB with focal adenocarcinoma is presented.

Isolated resection of the caudate lobe: indications, technique and results.

BACKGROUND/AIMS: This paper reports a series of 24 isolated caudate lobe resections (ICLR), performed for 13 benign tumors (10 hemangiomas, 2 focal nodular hyperplasias, 1 adenoma) and 11 malignant tumors (3 hepatocarcinomas, 1 peripheral cholangiocarcinoma and 7 metastatic - 5 colorectal carcinomas, 1 breast carcinoma, 1 adrenal carcinoma). Klatskin tumors were excluded. METHODOLOGY: There were 10 hemangioma enucleations, 7 Spiegel lobe resections and 7 high dorsal resections. Total vascular exclusion was performed in 7 cases. Vascular resection with reconstruction was necessary in 5 cases. RESULTS: Complications occurred in 7 cases (3 bile leaks, 3 abdominal fluid collections and one liver failure leading to death). From the 10 patients with malignant tumors who survived the operation, 7 developed recurrences: 2 intrahepatic, 1 retroperitoneal, 4 systemic. Five patients are alive (3 without recurrence). One patient died of multiple complications after a repeat hepatectomy and colectomy. Three patients died from generalized disease. Another patient, with generalized disease, was lost from follow-up. CONCLUSIONS: ICLR is a difficult operation, especially with malignant tumors. Total vascular exclusion of the liver is routinely recommended in high dorsal resection. Malignant tumors located in the caudate lobe have a poor prognosis; local and, especially, distant metastases are frequent. Aggressive chemotherapy and follow-up are recommended.

Gastrointestinal stromal tumors: retrospective analysis of the computer-tomographic aspects.

PURPOSE: To describe the computer-tomographic (CT) aspects of gastrointestinal stromal tumors (GISTs) in correlation to their histology. MATERIAL AND METHODS: The medical records of all patients at our hospital with a histologic diagnosis of GIST between January 2002 and June 2006, and investigated before surgery by CT, were reviewed. Two radiologists with knowledge of the diagnosis reviewed the CT findings. RESULTS: Amongst 15 cases of GISTs, 9 cases involved the stomach and 4 cases the small intestine. Location of the primary tumor could not be determined for 2 of 15 tumors, because of the presence of extensive peritoneal metastases. Most primary tumors were predominantly extraluminal (13 cases) while two were clearly endoluminal. The mean diameter of the primary tumor was 8 cm. The tumor margin was well defined in 12 patients and irregular in 3 cases. Central fluid attenuation was present in 11 tumors, while central gas was seen in two cases. Metastases were seen in 2 cases at presentation and in another 2 patients during follow-up. Spread was exclusive to the liver or peritoneum. Visceral obstruction was absent even in extensive peritoneal metastatic disease. Ascites was an unusual finding. CONCLUSIONS: CT plays an important role not only in the detection and the localization but also in the evaluation of the extension and follow-up of theses tumors. Using only CT aspects, we can only suspect the diagnosis to GISTs. Often other soft-tissue tumors with gastrointestinal involvement can mimic GISTs. In all cases histological diagnosis is essential.

Adrenalectomy for metastases from hepatocellular carcinoma - a single center experience.

BACKGROUND: Adrenal metastases (AM) from hepatocellular carcinoma (HCC) are rarely seen in clinical practice. The treatment is not standardized, the indications and efficacy of different therapeutic approaches being still controversial. PATIENTS: Between January 1995 and December 2005, 174 patients underwent liver resection for HCC in our center. AM were detected in four patients (2.3%): three of them had HCC and synchronous AM, and the remaining one developed AM 10 months after liver resection. All the patients with AM were treated by adrenalectomy (simultaneously with liver resection in synchronous metastases), followed by systemic chemotherapy. Non-resectable multifocal liver recurrences occurred in two patients, one of them having also a contralateral adrenal metastasis; these two patients are presently alive 26 and 43 months after adrenalectomy, respectively. Another patient died by liver recurrence 27 months postoperatively. The fourth patient is disease-free at 17 months after the initial operation. CONCLUSIONS: Adrenalectomy for AM from HCC should be performed whenever the primary tumor is well therapeutically controlled and the patient has a good performance status. Adrenalectomy offers the chance of more than 2 years survival in many patients. However, once AM are detected, the prognosis remains poor.

[Surgical treatment of liver metastases from colorectal cancer]. / Tratamentul chirurgical al metastazelor hepatice ale cancerului colo-rectal.

We analyze our experience over a 10-year period in the surgical treatment of liver metastases from colorectal cancer. Between 01.01.1995 and 08.31.2005 189 liver resections were performed in 171 patients with liver metastases from colorectal cancer (16 re-resections - 2 in the same patient and a "two-stage" liver resection in 2 patients). In our series there were 83 patients with synchronous liver metastases (69 simultaneous resections, 12 delayed resections and 2 "two-stage" liver resection were performed) and 88 metachronous liver metastases. Almost all types of liver resections have been performed. The morbidity and mortality rates were 17.4% and 4.7%, respectively. Median survival was 28.5 months and actuarial survival at 1-, 3- and 5-year was 78.7%, 40.4% and 32.7%, respectively. Between January 2002 and August 2005 hyperthermic ablation of colorectal cancer liver metastases has been performed in 6 patients; in other 5 patients with multiple bilobar liver metastases liver resection was associated with radiofrequency ablation and one patient underwent only radiofrequency ablation for recurrent liver metastasis. In conclusion, although the treatment of colorectal cancer liver metastases is multimodal (resection, ablation, chemotherapy and radiation therapy), liver resection is the only potential curative treatment. The quality and volume of remnant liver parenchyma is the only limitation of liver resection. The morbidity, mortality and survival rates after simultaneous liver and colorectal resection are similar with those achieved by delayed resection. Postoperative outcome of patients with major hepatic resection is correlated with the surgical team experience. The long-term survival was increased using the new multimodal treatment schemes.

[Current treatment of hepatocellular carcinoma. Analysis of a series of 123 cases over a 5-year period]. / Tratamentul multimodal al carcinomului hepatocelular. Analiza unei experiente clinice de 123 de cazuri în 5 ani.

We analyze a 123-cases experience over a 5-year period in the treatment of hepatocellular carcinoma (HCC). Liver resection, transplantation and hyperthermic ablation of the tumor were used according to the indication and patient selection. Systemic chemotherapy followed resection in 18 cases and hyperthermic ablation in 5 cases. Chemo-embolisation was performed in patients to be transplanted and in other two patients with tumor destruction. A number of 86 liver resections were performed in 84 patients (2 re- resections in 1 patient, subsequently transplanted) - 43 on normal liver and 41 on cirrhotic liver. Postoperative mortality was 4.7% in non-cirrhotic and 4.9% in cirrhotic patients. Survival in non-cirrhotic patients was 77% at 1 year, 65% at 2 years, and constant - 45% at 3 and 4 years, whereas in cirrhotic patients it was 60%, 56%, 56% and 36% (Kaplan-Meyer actuarial survival rates). Nine patients underwent liver transplantation (4 OLTs, 3 living donor LT, 1 split LT and 1 "domino" LT); postoperative mortality was 11% (1 patient). At present five patients are alive and well. One patient died by peritoneal carcinomatosis at 10 months; another patient died at 6 months by severe cholestatic recurrent C virus hepatitis and one patient was discharged with permanent severe neurologic disturbances. In 31 patients hyperthermic ablation of the tumor was used with zero mortality. Actuarial survival rates were 75% at one year and 67% at 2 years. In conclusion, in non-cirrhotic patients with HCC resection is the treatment of choice. In cirrhotic patients limited resections should be preferred and liver transplantation is the best solution in selected cases; local ablative methods may be used for some unresectable tumors. The role of adjuvant chemotherapy has to be determined in future comparative studies.